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1.
Adv Sci (Weinh) ; : e2408028, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382149

RESUMEN

Ovonic threshold switching (OTS) selectors based on amorphous chalcogenides can revolutionize 3D memory technology owing to their self-selecting memory (SSM) behavior. However, the complex mechanism governing the memory writing operation limits compositional and device optimization. This study investigates the mechanism behind the polarity-dependent threshold voltage shift (ΔVTH) through theoretical and experimental analyses. By examining the physical principles of threshold switching and conducting defect state analysis, the ΔVTH as a memory window is confirmed to be attributed to the dynamics of charged defects and their gradient near electrodes, influenced by the nonuniform electric field after threshold switching. This study provides critical insights into the operational mechanism of OTS-based SSM, known as selector-only memory, highlighting its advantages for developing high-density, low-cost, and energy-efficient memory technologies in the artificial intelligence era.

2.
Neural Regen Res ; 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39248160

RESUMEN

The neuroinflammatory response mediated by microglial activation plays an important role in the secondary nerve injury of traumatic brain injury. The post-transcriptional modification of N6-methyladenosine (m6A) is ubiquitous in the immune response of the central nervous system. The fat mass and obesity (FTO)-related protein catalyzes the demethylation of m6A modifications on mRNA and is widely expressed in various tissues, participating in the regulation of multiple diseases' biological processes. However, the role of FTO in microglial activation and the subsequent neuroinflammatory response after traumatic brain injury is unclear. In this study, we found that the expression of FTO was significantly down-regulated in both lipopolysaccharide-treated BV2 cells and a traumatic brain injury mouse model. After FTO interference, BV2 cells exhibited a pro-inflammatory phenotype as shown by the increased proportion of CD11b+/CD86+ cells and the secretion of pro-inflammatory cytokines. FTO-mediated m6A demethylation accelerated the degradation of ADAM17 mRNA, while silencing of FTO enhanced the stability of ADAM17 mRNA. Therefore, down-regulation of FTO expression leads to the abnormally high expression of ADAM17 in microglia. These results indicate that the activation of microglia and neuroinflammatory response regulated by FTO-related m6A modification plays an important role in the pro-inflammatory process of secondary injury following traumatic brain injury.

3.
Curr Med Chem ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39229988

RESUMEN

BACKGROUND: The Testis Expressed Metallothionein Like Protein (TESMIN) gene encodes highly conserved, cysteine-rich, low-molecular proteins that are activated by and have an affinity for heavy metal ions. Previous literature has shown its association with cancer. Nevertheless, no thorough bioinformatics analysis of TESMIN has been done yet in lung adenocarcinoma (LUAD). METHODS: Differential expression of TESMIN between cancer and normal tissues was confirmed by analyzing databases and immunohistochemistry staining. Enrichment analysis was adopted to explore biological functions. The relationship of TESMIN with immune infiltration was evaluated by ssGSVA, with immunotherapy response predicted by TCIA and TIDE tools, with mutational traits analyzed by R software. Drug sensitivity analysis was implemented via GSCA tool, pRRophetic algorithms, and CellMiner database. RESULTS: The results demonstrated that TESMIN expression was upregulated in tumor tissue and related to Ki67. TESMIN was associated with poor survival and significantly related to age, gender, N stage, M stage, pathological stage, and survival status. TESMIN- related genes (TRGs) were primarily involved in cell division and cancer-related enrichment pathways. TESMIN was associated with high frequencies of somatic mutations and an immunosuppressive tumor microenvironment. Interestingly, patients with elevated levels of TESMIN expression benefited more from commonly used chemotherapy drugs such as cisplatin, paclitaxel, vinorelbine, and docetaxel, whereas those with low levels of TESMIN expression showed favorable clinical responses to immunotherapy. CONCLUSION: As a prognostic biomarker associated with the cell cycle and immune infiltration, TESMIN may serve as an effective target for predicting the sensitivity to immunotherapy and chemotherapy.

4.
New Phytol ; 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39279041

RESUMEN

Chromatin immunoprecipitation and sequencing (vs ChIP-seq) is an essential tool for epigenetic and molecular genetic studies. Although being routinely used, ChIP-seq is expensive, requires grams of plant materials, and is challenging for samples that enrich fatty acids such as seeds. Here, we developed an Ultrasensitive Plant ChIP-seq (UP-ChIP) method based on native ChIP-seq combined with Tn5 tagmentation-based library construction strategy. UP-ChIP is generally applicable for profiling both histone modification and Pol II in a wide range of plant samples, such as a single Arabidopsis seedling, a few Arabidopsis seeds, and sorted nuclei. Compared with conventional ChIP-seq, UP-ChIP is much less labor intensive and only consumes 1 µg of antibody and 10 µl of Protein-A/G conjugated beads for each IP and can work effectively with the amount of starting material down to a few milligrams. By performing UP-ChIP in various conditions and genotypes, we showed that UP-ChIP is highly reliable, sensitive, and quantitative for studying histone modifications. Detailed UP-ChIP protocol is provided. We recommend UP-ChIP as an alternative to traditional ChIP-seq for profiling histone modifications and Pol II, offering the advantages of reduced labor intensity, decreased costs, and low-sample input.

5.
Front Microbiol ; 15: 1452798, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39224214

RESUMEN

Sweet sorghum can be used to produce a substantial quantity of biofuel due to its high biological yield and high carbohydrate content. In this study, we investigated the dynamic changes in fermentation characteristics, carbohydrate components, and the bacterial community during the ensiling of wilted and unwilted sweet sorghum. The results revealed a rapid fermentation pattern and high-quality fermentation quality in wilted and unwilted sweet sorghum, wherein lactic acid, and acetic acid accumulated and stabilized during the initial 9 days of ensiling, with the pH values less than 4.2, until 60 days of ensiling. We found that the ensiling of sweet sorghum involved the degradation (5% ~ 10%) of neutral detergent fiber (NDF) and hemicellulose and that the degradation of NDF fit a first-order exponential decay model. A shift in dominance from Lactococcus to Lactobacillus occurred before the first 9 days of ensiling, and the abundance of Lactobacillus (r = -0.68, p < 0.001) was negatively correlated with the NDF content. The relative abundances of Lactobacillus in wilted and unwilted sweet sorghum after ensiling for 60 days were 76.30 and 93.49%, respectively, and relatively high fermentation quality was obtained. In summary, ensiling is proposed as a biological pretreatment for sweet sorghum for subsequent biofuel production, and unlike other materials, sweet sorghum quickly achieves good fermentation quality and has great potential for bioresource production.

6.
Materials (Basel) ; 17(18)2024 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-39336390

RESUMEN

Direct current (DC) and pulsed DC tungsten inert gas (TIG) additive manufacturing processes were employed to fabricate GH4169 high-temperature alloy specimens. Upon comparing and analysing the two additive manufacturing methods, the evolution of microstructure and mechanical properties of the additively manufactured specimens were discussed. It provided a useful reference for the engineering application of pulsed DC TIG technology. The results showed that the overall forming process of the specimen was relatively stable under the DC TIG additive manufacturing and pulsed DC TIG additive manufacturing processes. The aspect ratio of the deposited layer of the pulsed DC-deposited specimen was relatively low, and the deposited layer of the pulsed DC specimen became flatter, which was conducive to maintaining the stability of the molten pool during the deposition process and improving forming accuracy. The microstructure distribution of the deposited layer from bottom to top was relatively uneven, with columnar dendrites in the bottom layer, cellular crystals in the middle layer, and equiaxed crystals in the top layer. Compared with the DC TIG additive manufacturing of GH4169 high-temperature alloy specimens, the Laves phase of the pulsed DC specimens was significantly reduced, which improved the plasticity and brittleness of the material.

7.
Sensors (Basel) ; 24(18)2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39338697

RESUMEN

Due to the limitations of deep learning models in processing one-dimensional signal feature extraction, and high model complexity leading to low training accuracy and large consumption of computing resources, this paper innovatively proposes a rolling bearing fault diagnosis method based on Gramian Angular Field (GAF) and enhanced lightweight residual network. Firstly, the one-dimensional signal is transformed into a two-dimensional GAF image, fully preserving the signal's temporal dependency. Secondly, to address the parameter redundancy and high computational complexity of the ResNet-18 model, its residual blocks are improved. The second convolutional layer in the downsampling residual blocks is removed, traditional convolutional layers are replaced with depthwise separable convolutions, and the lightweight Efficient Channel Attention (ECA) module is embedded after each residual block. This further enhances the model's ability to capture key features while maintaining low computational cost, resulting in a lightweight model referred to as E-ResNet13. Finally, the generated GAF feature maps are fed into the E-ResNet13 model for training, and through a global average pooling layer, they are mapped to a fully connected layer for classifying the faults of rolling bearings. Verifying the superiority of the proposed GAF-E-ResNet13 model, experimental results show that the GAF image encoding method achieves higher fault recognition accuracy compared to other encoding methods. Compared with other intelligent diagnosis methods, the E-ResNet13 model demonstrates strong diagnostic performance and generalization capability under both a single condition and complex varying conditions, fully proving the innovation and practicality of this method.

8.
Neuroimage ; 300: 120850, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39260782

RESUMEN

Non-invasive myelin water fraction (MWF) and g-ratio mapping using microstructural MRI have the potential to offer critical insights into brain microstructure and our understanding of neuroplasticity and neuroinflammation. By leveraging a unique panel of variably hypomyelinating mouse strains, we validated a high-resolution, model-free image reconstruction method for whole-brain MWF mapping. Further, by employing a bipolar gradient echo MRI sequence, we achieved high spatial resolution and robust mapping of MWF and g-ratio across the whole mouse brain. Our regional white matter-tract specific analyses demonstrated a graded decrease in MWF in white matter tracts which correlated strongly with myelin basic protein gene (Mbp) mRNA levels. Using these measures, we derived the first sensitive calibrations between MWF and Mbp mRNA in the mouse. Minimal changes in axonal density supported our hypothesis that observed MWF alterations stem from hypomyelination. Overall, our work strongly emphasizes the potential of non-invasive, MRI-derived MWF and g-ratio modeling for both preclinical model validation and ultimately translation to humans.


Asunto(s)
Imagen por Resonancia Magnética , Proteína Básica de Mielina , Vaina de Mielina , Sustancia Blanca , Animales , Vaina de Mielina/metabolismo , Ratones , Proteína Básica de Mielina/metabolismo , Proteína Básica de Mielina/genética , Imagen por Resonancia Magnética/métodos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/metabolismo , Masculino , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Procesamiento de Imagen Asistido por Computador/métodos , Femenino
9.
ACS Omega ; 9(37): 38925-38935, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39310199

RESUMEN

During polar navigation, adverse environmental conditions like cold temperatures, fatigue, and corrosion can affect surface and underwater manned vehicles (UMVs). Understanding the fatigue fracture growth behavior of polar ship steel is crucial for ensuring safety. This study investigates the mechanical properties and fatigue fracture propagation of steel used in underwater vehicle rudders under various low-temperature conditions through experimental research. It compares and analyzes the static mechanical characteristics, fatigue crack growth rate, and fracture morphology of underwater manned vehicle rudder steels at different low temperatures. Findings show enhancements in yield strength, tensile strength, elastic modulus, and fatigue crack propagation life of steel 925A, steel 20#, and their welded parts under low-temperature conditions. The tensile strength of 925A steel, 20# steel, and their welded parts increases by 6.87%, 14.61%, and 12.55%, respectively, as the temperature decreases from 20 to -60 °C. The yield strength also increases by 14.17%, 29.09%, and 15.76%, respectively. Fatigue crack propagation rate experiments were conducted under different constant low-temperature conditions. This study offers direction for future modeling and experimental testing.

10.
Exp Ther Med ; 28(5): 427, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39301250

RESUMEN

The gut microbiota refers to the diverse bacterial community residing in the gastrointestinal tract. Recent data indicate a strong correlation between alterations in the gut microbiota composition and the onset of various diseases, notably cardiovascular disorders. Evidence suggests the gut-cardiovascular axis signaling molecules released by the gut microbiota play a pivotal role in regulation. This review systematically delineates the association between dysbiosis of the gut microbiota and prevalent cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction and heart failure. Furthermore, it provides an overview of the putative pathogenic mechanisms by which dysbiosis in the gut microbiota contributes to the progression of cardiovascular ailments. The potential modulation of gut microbiota as a preventive strategy against cardiovascular diseases through dietary interventions, antibiotic therapies and probiotic supplementation is also explored and discussed within the present study.

11.
J Med Chem ; 67(17): 15620-15675, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39172133

RESUMEN

Acinetobacter baumannii, a commonly multidrug-resistant Gram-negative bacterium responsible for large numbers of bloodstream and lung infections worldwide, is increasingly difficult to treat and constitutes a growing threat to human health. Structurally novel antibacterial chemical matter that can evade existing resistance mechanisms is essential for addressing this critical medical need. Herein, we describe our efforts to inhibit the essential A. baumannii lipooligosaccharide (LOS) ATP-binding cassette (ABC) transporter MsbA. An unexpected impurity from a phenotypic screening was optimized as a series of dimeric compounds, culminating with 1 (cerastecin D), which exhibited antibacterial activity in the presence of human serum and a pharmacokinetic profile sufficient to achieve efficacy against A. baumannii in murine septicemia and lung infection models.


Asunto(s)
Transportadoras de Casetes de Unión a ATP , Infecciones por Acinetobacter , Acinetobacter baumannii , Antibacterianos , Proteínas Bacterianas , Lipopolisacáridos , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/metabolismo , Antibacterianos/farmacología , Antibacterianos/química , Animales , Lipopolisacáridos/metabolismo , Lipopolisacáridos/antagonistas & inhibidores , Ratones , Humanos , Proteínas Bacterianas/antagonistas & inhibidores , Proteínas Bacterianas/metabolismo , Transportadoras de Casetes de Unión a ATP/antagonistas & inhibidores , Transportadoras de Casetes de Unión a ATP/metabolismo , Infecciones por Acinetobacter/tratamiento farmacológico , Infecciones por Acinetobacter/microbiología , Pruebas de Sensibilidad Microbiana
12.
J Med Chem ; 67(17): 15807-15815, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39146536

RESUMEN

Targeted protein degradation through the lysosomal pathway has attracted increasing attention and expanded the scope of degradable proteins. However, the endogenous lysosomal degradation strategies are mainly based on antibodies or nanobodies. Effective small molecule lysosomal degraders are still rather rare. Herein, a new lysosomal degradation approach, termed peptide-mediated small molecule lysosome-targeting chimeras (PSMLTACs), was developed by the incorporation of small molecule ligands with a lysosome-sorting NPGY motif containing the cell-penetrating peptide. PSMLTACs were successfully applied to degrade both membrane and intracellular targets. In particular, the PSMLTAC strategy demonstrated higher degradation efficiency on membrane target PD-L1 and intracellular target PDEδ than corresponding PROTAC degraders. Taken together, this proof-of-concept provides a convenient and effective strategy for targeted protein degradation.


Asunto(s)
Lisosomas , Proteolisis , Lisosomas/metabolismo , Humanos , Proteolisis/efectos de los fármacos , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/metabolismo , Péptidos de Penetración Celular/farmacología , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/metabolismo , Antígeno B7-H1/metabolismo , Antígeno B7-H1/antagonistas & inhibidores , Péptidos/química , Péptidos/farmacología , Péptidos/metabolismo
13.
Endocr Rev ; 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39116368

RESUMEN

Somatostatin analogs, such as octreotide (OCT), lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly. These ligands are also used as important molecules for radiation therapy and imaging of neuroendocrine tumors (NETs). Somatostatin receptors (SSTRs) are canonical G protein-coupled proteins (GPCRs) that play a role in metabolism, growth, and pathological conditions such as hormone disorders, neurological diseases, and cancers. Cryogenic electron microscopy (cryo-EM) combined with the protein structure prediction platform AlphaFold has been used to determine the three-dimensional structures of many proteins. Recently, several groups published a series of papers illustrating the three-dimensional structure of SSTR2, including that of the inactive/activated SSTR2-G protein complex bound to different ligands. The results revealed the residues that contribute to the ligand binding pocket and demonstrated that Trp8-Lys9 (the W-K motif) in somatostatin analogs is the key motif in stabilizing the bottom part of the binding pocket. In this review, we discuss the recent findings related to the structural analysis of SSTRs and SRLs, the relationships between the structural data and clinical findings, and the future development of novel structure-based therapies.

14.
ERJ Open Res ; 10(4)2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39104963

RESUMEN

Study question: In large multinational patient surveys, spirometry (which requires repeated, reproducible maximal efforts) can be associated with cough, breathlessness and tiredness, particularly in those with idiopathic pulmonary fibrosis (IPF). Oscillometry is an effort-independent test of airways resistance and reactance. We hypothesised that oscillometry would take less time to perform and would be associated with reduced symptom burden than spirometry. Patients and methods: Spirometry and oscillometry were performed in 66 participants with IPF and repeated 2 weeks later. We compared time taken to perform tests, symptom burden and test-retest reliability with Bland-Altman plots and intraclass correlation coefficients (ICCs). Results: Oscillometry took significantly less time to perform than spirometry (mean -4.5 (99% CI -6.0 to -3.0) min) and was associated with lower symptom burden scores for cough (-1.3, 99% CI -1.7 to -0.8), breathlessness (-1.0, 99% CI -1.4 to -0.5), and tiredness (-0.5, 99% CI -0.9 to -0.2). On Bland-Altman analysis, all measures showed good agreement, with narrow limits of agreement and the mean bias lying close to 0 in all cases. The ICCs for forced expiratory volume in 1 s and forced vital capacity were 0.94 and 0.89, respectively, and ranged between 0.70 and 0.90 for oscillometry measures. Conclusion: Oscillometry is quicker to perform and provokes less symptoms than spirometry in patients with IPF.

15.
Zhen Ci Yan Jiu ; 49(7): 767-776, 2024 Jul 25.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-39020496

RESUMEN

Stroke brings the pathological changes of brain tissues such as hematoma formation or ischemia and hypoxia, which leads to neuronal death and axon degeneration. Axon regeneration after its injury is mainly dependent on the surrounding microenvironment and the related proteins, including glial scar, myelin associated inhibitory factors, axon guidance molecules, and neurotrophic factors. All of them affect axon growth by regulating the morphology and orientation of growth cones, the synaptic stability, and the proliferation and differentiation of neural stem cells. This article summarizes the mechanism of acupuncture in regulating axon regeneration after stroke. Acupuncture inhibits glial scar formation, alleviates the inhibitory effects of its physical and chemical barriers on axon growth, reverses the inhibitory effects of myelin-related inhibitory factors on axon growth, and adjusts the level of axon guidance molecules to promote the proliferation and differentiation of neural stem cells and the regeneration of injured axons, and up-regulates neurotrophic factors. Eventually, post-stroke nerve injury can be ameliorated.


Asunto(s)
Terapia por Acupuntura , Axones , Regeneración Nerviosa , Accidente Cerebrovascular , Humanos , Animales , Axones/metabolismo , Axones/fisiología , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/fisiopatología , Células-Madre Neurales/metabolismo
16.
PLoS One ; 19(7): e0307113, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39008477

RESUMEN

Understanding the extent of inflammation is crucial for early disease detection, monitoring disease progression, and evaluating treatment responses. Over the past decade, researchers have demonstrated the need to understand the extent of inflammation through qualitative or quantitative characterization of tissue viscoelasticity using different techniques. In this scientific review, an examination of research on the association between elasticity and Viscosity in diseases, particularly as tissue inflammation progresses, is conducted. A review of utilizing mechanical rheological models to characterize quantitative viscoelastic parameters of normal and inflamed tissues is also undertaken. Based on inclusion and exclusion criteria, we identified 14 full-text studies suitable for review out of 290 articles published from January 2000 to January 2024. We used PRISMA guidelines for the systematic review. In the review, three studies demonstrated the criterion used by the researchers in identifying the best rheological model. Eleven studies showed the clinical application of the rheological model in quantifying the viscoelastic properties of normal and pathological tissue. The review quantified viscoelastic parameters for normal and pathological tissue across various soft tissues. It evaluated the effectiveness of each viscoelastic property in distinguishing between normal and pathological tissue stiffness. Furthermore, the review outlined additional viscoelastic-related parameters for researchers to consider in future stiffness classification studies.


Asunto(s)
Elasticidad , Inflamación , Reología , Viscosidad , Humanos , Inflamación/patología , Modelos Biológicos
17.
Neuro Oncol ; 2024 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-38989697

RESUMEN

BACKGROUND: Managing non-functioning pituitary adenomas (NFPAs) is difficult due to limited drug treatments. Cabergoline's (CAB) effectiveness for NFPAs is debated. This study explores the role of HTR2B in NFPAs and its therapeutic potential. METHODS: We conducted screening of bulk RNA-sequencing data to analyze HTR2B expression levels in NFPA samples. In vitro and in vivo experiments were performed to evaluate the effects of HTR2B modulation on tumor growth and cell cycle regulation. Mechanistic insights into the HTR2B-mediated signaling pathway were elucidated using pharmacological inhibitors and molecular interaction assays. RESULTS: Elevated HTR2B expression was detected in NFPA samples, which was associated with increased tumor survival. Inhibition of HTR2B activity resulted in the suppression of tumor growth through modulation of the G2M cell cycle. The inhibition of HTR2B with PRX-08066 was found to block STAT3 phosphorylation and nuclear translocation by interfering with the Gαq/PLC/PKC pathway. A direct interaction between PKC-γ and STAT3 was critical for STAT3 activation. CAB was shown to activate pSTAT3 via HTR2B, reducing its therapeutic potential. However, the combination of an HTR2B antagonist with CAB significantly inhibited tumor cell proliferation in HTR2B-expressing pituitary tumor cell lines, a xenografted pituitary tumor model, and patient-derived samples. Analysis of patient-derived data indicated that a distinct molecular pattern characterized by upregulated HTR2B/PKC-γ and downregulated BTG2/GADD45A may benefit from combination treatment with CAB and PRX-08066. CONCLUSIONS: HTR2B is a potential therapeutic target for NFPAs, and its inhibition could improve CAB efficacy. A dual therapy approach may be beneficial for NFPA patients with high HTR2B expression.

18.
Materials (Basel) ; 17(13)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38998312

RESUMEN

The production of aluminum alloy multi-lumen tubes primarily involves hot bending formation, a process where controlling thermal deformation quality is difficult. Specifically, the inner cavity wall of the tube is prone to bending instability defects under the bending stress field. To address these challenges in the bending deformation of aluminum alloy multi-lumen tubes, a multi-lumen liquid-filled bypass forming method is proposed in this paper. This study focuses on the 6063-T5 aluminum alloy double-lumen tube as the research object. The liquid-filled bending deformation behavior of the aluminum alloy double-lumen tube was investigated, and the deformation theory of the aluminum alloy double-lumen tube was studied. Through experimental and numerical simulation methods, the influence of support internal pressure, bending radius, and tube wall thickness on the liquid-filled bending deformation behavior of the double-lumen tube was examined. The results indicate that when the value of internal pressure was 7.5 MPa, the straightening of the outer wall was improved by 2.51%, the thinning rate of wall thickness was minimized, and the internal concave defect was effectively suppressed. The liquid-filled bending method provides a promising new approach for the integrated bending and forming of multi-lumen tubes.

19.
Toxicol Lett ; 399: 1-8, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38969027

RESUMEN

2-Methyl-4-nitroaniline (MNA), an intermediate in the synthesis of azo dyes, is widely distributed in various environmental media and organisms. Although there is speculation regarding MNA's potential to be hepatotoxic, the underlying mechanisms of its hepatotoxicity and its definitive diagnostic process remain largely unexplored. In this research. In the present study, we initially predicted the toxicity and possible toxic effect pathways of MNA using ProTox-II, and found that MNA binds to the PPARγ receptor (binding energy -6.118 kcal/mol) with a potential PPARγ agonist effect. Subsequently, in vivo exposure evaluation was conducted on Wistar rats to assess the impact of MNA after a 90-day exposure period, by detecting serum biochemical indexes, hematological indexes, urinary indexes, inflammatory factors, liver histopathological observations and liver tissue PPARγ mRNA expression. The results showed that MNA causes liver function abnormalities, liver histopathological changes and inflammatory response, along with a pronounced increase in PPARγ mRNA levels. This study suggests that the hepatotoxic mechanism of MNA may be related to its possible upregulation of PPARγ expression, increased liver dysfunction and inflammatory responses. Based on these results, the benchmark dose lower limit (BMDL) of 1.503 mg/kg for male Wistar rats was also established, providing a vital benchmark for determining the safety threshold of MNA. Our data highlight the hepatotoxic mechanism of MNA and contribute to a better understanding of its potential etiological diagnosis.


Asunto(s)
Compuestos de Anilina , Enfermedad Hepática Inducida por Sustancias y Drogas , Hígado , PPAR gamma , Ratas Wistar , Animales , Compuestos de Anilina/toxicidad , Masculino , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Administración Oral , PPAR gamma/genética , PPAR gamma/metabolismo , Ratas , Simulación del Acoplamiento Molecular , Relación Dosis-Respuesta a Droga
20.
Diabetes Metab Syndr Obes ; 17: 2619-2625, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38974951

RESUMEN

Purpose: To examine the risk of type 2 diabetes mellitus in non-obese patients with pancreatic fatty infiltration through abdominal computed tomography (CT) quantitation. Patients and Methods: We carried out a retrospective analysis of abdominal CT and inpatient medical records of 238 inpatients from July 2019 to April 2021. The patients were divided into a normal non-obese group (BMI < 25, n = 135) and diabetic non-obese group (BMI < 25, n = 103). Abdominal CT-related parameters included body width; mean CT values of the pancreas, liver, and spleen; difference between pancreas and spleen CT values (P-S); pancreas-to-spleen attenuation ratio (P/S); and liver-to-spleen attenuation ratio (L/S). Logistic regression was used to estimate the risk factors for comorbid diabetes in a non-obese population. Results: The P-values of the pancreas CT value, P-S, P/S, body width, and L/S were all <0.05 and correlated to comorbid diabetes in non-obese patients. Worsening pancreatic fatty infiltration increased the risk of developing diabetes. Using a P/S of 1.0 as reference, every successive decrease in this ratio by 0.1 increases patient risk by 3.981, 4.452, 6.037, and 12.937 times. Conclusion: The risk of developing type 2 diabetes mellitus in non-obese patients increases with the degree of pancreatic fatty infiltration as assessed by CT.

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